This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Asthma is a highly prevalent disease and a significant cause of morbidity and mortality in the pediatric population. Preventive strategies have principally focused on allergen avoidance to prevent sensitization leading to the development of atopy and asthma. Sensitization commonly occurs during preschool years;the earlier it occurs, the more severe are the long-term consequences. Recent studies suggest that reduction of allergic sensitization during early childhood may be an effective strategy for asthma prevention. For example, the Preventive Allergy Treatment (PAT) study demonstrated that the progression of allergic rhinitis to asthma can be reduced by conventional (subcutaneous) immunotherapy in children 6-14 years of age. In another study, Passalacqua et al. showed that sublingual immunotherapy resulted in a major reduction in new sensitizations in the treatment group. Additionally,, the International Study of Asthma and Allergies in Childhood (ISAAC) has identified an inverse relationship between levels of pollen exposure in early life and allergy symptoms, suggesting that heightened mucosal exposure to the allergen may provide protection against sensitization. Sublingual immunotherapy has been shown to be safe in children, and no severe systemic adverse event has been reported in the literature in more than 15 years. Therefore, this trial aims to optimize the mucosal tolerance process by sublingual immunotherapy, which enhances the level of allergen exposure via the oral mucosa, a route that has been shown to be preferentially tolerogenic. HYPOTHESIS: Sublingual immunotherapy with an inhalant allergen mixture can prevent the development of allergic sensitization and asthma in high-risk children.